The Next Wave in Performance Enhancement

It’s January, and many of us are trying to achieve a better version of ourselves. Professional athletes are no different, although their goals probably involve enhanced performance on the field. But professional athletes are just as susceptible to snake oil salesmen peddling their wares as we can sometimes can be. If a baseball player is looking to improve his performance with effective measures, but also steer clear of banned substances and potential harm, what are his options?

I set out to explore what might be on the horizon with regards to performance enhancement. But first, we need to be aware of what players can’t do. The current list of prohibited substances in the MLB Joint Drug Agreement is a long list of don’ts. These include drugs of abuse, performance enhancing substances, stimulants, and diuretics and masking agents. It’s based upon the World Anti-Doping Agency (WADA) list, with input from professionals selected by MLB and the MLBPA. These prohibitions aren’t meant to come at the expense of keeping players healthy and active on the field—or extending their playing careers. The therapeutic use exemption (TUE) can play a role in striking this balance, as a player with a confirmed medical need can receive a medication on the prohibited substances list.

By excluding specific things, we leave open a wide arena of things that a) aren’t banned, and b) may or may not improve performance. We haven’t really defined performance per se, or a degree or type of enhancement. And when it comes to the “performance enhancing substances” that are actually on the prohibited list, we need to note that there isn’t always evidence that these “performance enhancing substances” actually enhance anything except for urine.

Whether these prohibited substances are actually performance enhancing substances is a discussion for another day, but it does provide a framework for our discussion today. What is performance, and how can it be enhanced? What exactly is the threshold for enhancement? And yes, we even need to ask, what is a substance? Once we look away from the list of prohibited substances, and consider what isn’t prohibited, we see we have a lot of leeway when it comes to looking for the next performance enhancing substance.

We can narrow things down a bit. For instance, we always have to weigh the benefit and risk involved with each intervention. The benefits are obvious, of course—we’re enhancing performance and making ourselves better baseball players! But again, what exactly do we mean by “performance enhancing”?

Enhanced performance might present itself as better play on the field, which could come in the form of cognitive enhancement, added strength, and reduced reaction times. But performance enhancement should also include anything that will reduce the time lost to injuries, or the severity of injuries. We don’t even know what our baseline is—does a performance enhancer enhance your own personal, natural performance, so that you are a better version of yourself? Or does a performance enhancer simply put you on par with a replacement level player? Another way to look at it—the threshold for improving Bryce Harper’s performance is pretty high, whereas improving the author’s performance is a really low bar, because she is extremely unathletic. So what might be a performance enhancing drug for me, might have absolutely no effect on Bryce Harper.

We also have to consider that the phrase “performance enhancing” commonly precedes the word “drug.” In fact, the phrase “performance enhancing drugs” has become such an integral part of the sports lexicon that the abbreviation PEDs is used routinely, with little consideration for what the phrase actually means. The actual terminology used in MLB’s Joint Drug Agreement is “performance enhancing substances.” You could argue that this isn’t limited to drugs that one might ingest or inject, but should also include devices and other interventions.

Taking the nebulous nature of the term “performance enhancement” into consideration, we’ll start with something as basic as fuel. Improving one’s diet and nutrition isn’t an illegal performance enhancer, and there’s evidence that modifying one’s diet can be beneficial. It’s probably not as significant as a certain former Montreal Expos draftee would have you believe, but it’s not prohibited and it’s low risk. In addition to working with team nutritionists and chefs, some players turn to dietary supplements to give their nutritional intake a boost, with the hopes that they’ll enjoy a performance boost as well. Dietary supplements aren’t prohibited by MLB, although players are advised to only take NSF Certified for Sport supplements, as dietary supplements are not regulated for purity or efficacy.

One category of dietary supplement is probiotics—“good” bacteria which allegedly can enhance digestion —metabolism, immunity, and offer protection from “bad” bacteria. Asked for comment regarding probiotics, an MLB spokesperson noted: “With respect to all nutritional and dietary supplements, as now described in Article XIII.K of the Basic Agreement, all MLB Clubs are required to provide to players certain categories of NSF Certified for Sport nutrition supplements to players during the season and off-season. This includes pre- and probiotic digestive aid supplements. Clubs are not permitted to recommend or provide any supplements that are not NSF Certified for Sport.”

There are a number of commercially available, NSF Certified for Sport probiotics that purport to reduce inflammation, provide protection against pathogens, and more efficiently convert fiber into energy. Since they’re not prohibited, and may provide a boost, it wouldn’t be surprising if athlete were taking the supplements. But like many supplements, there is a lack of rigorous data suggesting that there are benefits to taking probiotics.

But, let’s take that one step further. We know that an athlete has dietary needs that exceed those of the average human being. What if athletes derive a benefit from probiotics the general population does not?

Although there is little evidence to support a therapeutic effect of probiotic supplements in the general population, there is evidence that an athlete’s gut flora—microbiome—is quite different from the average human being’s. And there’s evidence that athletes who compete in similar sports have similar gut bacteria: “This suggests that certain factors—such as performing high levels of cardiovascular exercise or spending large amounts of time in the ocean—may affect the makeup of our microbiomes dramatically.” In turn, it suggests that there might be a general gut flora profile shared among professional baseball players.

Perhaps that microbiome does have an effect on athletes’ overall performance—it may enable them to process nutrients more efficiently, or protect them from certain sport-specific maladies. Researchers have found that “extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in fecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle.” This microbial diversity reflects increases in amino acid biosynthesis and carbohydrate metabolism. Researchers also found observed differences in microbial metabolites, particularly the short chain fatty acids acetate, propionate, and butyrate, which may be associated with enhanced muscle turnover and overall health.

But we’re faced with a chicken-and-egg scenario: which came first, the athletes, or their microbiome? Is the athlete’s microbiome simply the result of diet, which is itself very different from an average human’s diet? Does an athlete’s microbiome reflect years of specialized training? It’s a great example of how not to conflate correlation and causation. It’s much more likely that the athletes’ microbiome is the result of their roles as athletes—their diet, their training—and not an inherent feature that would lead them down the path to professional athleticism.

Regardless of the origins of this athletic microbiome, or whether it’s indicative of anything really, sports genomics researchers at the Wyss Institute have started the company Fitbiomics in the hopes of developing specialized probiotic supplements based on an athlete’s microbiome. Perhaps by analyzing a high performance athlete’s microbiome, you’ll be able to create the same microbial environment in your own gut—and perhaps that will lead to athletic performance similar to the athlete whose microbiome you’re trying to replicate. Fitbiomics’ ultimate goal is to enter the nutraceuticals market with a specialized probiotic product designed for athletes.

Of course, until this tailor-made probiotic is commercially available, there’s always the do-it-yourself approach. This can be accomplished using equipment you have in your own kitchen—all you need is an enema kit and fecal matter from your favorite athlete. (You’d probably need to get permission from Bryce Harper before you take a stool sample for yourself, though.)

While it’s tempting to think that you can improve your athletic ability by tweaking your microbiome so that it looks more like your favorite player’s microbiome, there’s limited evidence regarding the efficacy of probiotics, or specialized fecal transplants. While fecal transplants are mostly used in the medical realm for the treatment of Clostidrium difficile infections—and even then, it should be noted that fecal matter transplants are used sparingly, as there’s still a stigma associated with the procedure—it’s not going to happen in baseball anytime soon. We don’t know how effective they are as a performance enhancer, and it’s highly unlikely that a poop transplant is going to propel someone from Low-A to the majors more quickly than he would move without the microbiotic supplement. But, as noted by Bryan White, Director of Microbiome Projects in the Division of Nutritional Sciences at the University of Illinois, the lack of rigorous scientific evidence may not stop athletes from poop doping: “Will athletes do it? If they think they can get something out of it they’ll do it.”

So, fecal matter transplants and specialized probiotics are probably not going to provide a boost in performance, but a PED—performance enhancing diet—might be beneficial. There’s also another type of PED we should consider—a performance enhancing device. In one sense, MLB has already prohibited certain devices that one might consider performance enhancing devices—say, a corked bat, or the technological means of stealing signs. But there is very little guidance regarding medical devices.

Again, we need to consider the definition of “performance” and “enhancing.” There are other interventions and technologies that could serve as performance enhancers, but aren’t prohibited substances or devices. Taking a very broad view of the idea of a “performance enhancer,” you could consider almost anything that corrects inherent deficiencies to fall under the category. For instance, pacemakers and insulin injection devices help the body perform more effectively. Indeed, Jason Johnson and now Adam Duvall played while using an insulin pump for their Type I diabetes.

Another example would be corrective lenses for improving one’s eyesight. Poor eyesight is completely normal and very common. Of Americans between the ages of 12-54, 42 percent have myopia, otherwise known as nearsightedness. In essence, contact lenses are a performance enhancer. While these require a doctor’s prescription, a baseball player doesn’t need to get a therapeutic use exemption to wear them on the field. MLB isn’t about to deny a player access to eyeglasses or contact lenses! If the term is understood broadly, contact lenses are a performance enhancing device.

Let’s take this idea one step further. Beyond corrective lenses, there are other tools at an ophthalmologist’s disposal for correcting eyesight, namely, laser eye surgery, such as laser in-situ keratomileusis, commonly known as LASIK. The LASIK procedure is fairly common now, and can provide improvements to eyesight that may not be achieved through the use of corrective lenses. LASIK has the potential to change one’s eyesight to make it even better than 20/20, which is what is considered normal or standard. You may even achieve 20/10 vision; in other words, what a normal person can see from 10 feet away, you can see from 20 feet.

The improvement to vision itself is a tremendous benefit, but let’s not neglect the hassle of contact lenses. They can be drying, scratchy, and uncomfortable. If you’re standing in an area where there’s a lot of dirt being kicked around—say, a baseball infield—you run the risk of having particulates irritate your eyes.

Freddie Freeman is a player who wore contact lenses and also had dry eye issues. Dry eye is uncomfortable and can hinder eyesight, which in turn could hinder performance at the plate. A further complication in Freeman’s case: repeatedly replacing his contact lenses led him to scratching his cornea. Eventually, Freeman opted for LASIK to correct his vision. Being able to see more clearly may affect a player’s game; Wilson Ramos appeared to have a resurgence at the plate after having LASIK.

While the benefits to a hitter are immediately obvious—an ability to identify a pitch as it comes in that much sooner—a pitcher may benefit as well. Greg Maddux underwent the LASIK eye procedure, and noted that without correction, “I could see the catcher, but I wasn’t sure who was catching me.”

While laser eye surgery isn’t without risk, these have minimized; even dry eye, a common complaint among people who have had LASIK procedures, can be remedied using eye drops or tear duct procedures.

Eye surgery is hardly the most common surgical procedure among baseball players. We’re all familiar with the dreaded ulnar collateral ligament reconstruction, commonly known as Tommy John surgery. The procedure replaces a torn ulnar collateral ligament from the forearm, and replaces it with a tendon, typically removed from the player’s arm or leg, or perhaps a cadaver.

“We can rebuild him, we have the technology” isn’t just a catchphrase from The Six Million Dollar Man; UCL reconstruction is an artificial way of prolonging someone’s career, and should be considered in a discussion of performance enhancement. There is nothing natural about Tommy John surgery, but this common procedure is part of baseball’s lexicon and widely accepted. As Jon Roegele noted entering the 2018 season, “Roughly seven out of every eight MLB games you watched last year involved a pitcher whose career has been extended due to this surgery. More than a quarter of current major league pitchers have had it.”

It’s not performance enhancement per se—players generally don’t see an improvement upon their pre-surgery performance. But given the nebulous definition of “performance” and “enhancement,” if we compared post-surgical results to the results that would occur if there was no surgery, I think we can agree that a player who is actively pitching is performing better than a player whose career was ended by a torn UCL.

We also need to note that the procedure of today is vastly different from the procedure as first performed by Dr. Frank Jobe on the eponymous Tommy John. The mechanism by which the new ligament is attached has modernized. In addition to sutures and screws, which may be made of a variety of materials, synthetic adhesives and glues may be used. And what if you were to use a synthetic, lab-grown tendon? What about a 3D printed synthetic tendon? Where do we draw the line between an intervention that merely corrects a deficiency or repairs an injury, and a performance enhancing one?

To answer this, we need to consider what is inherent. Poor eyesight and the inability to adequately regulate insulin output are clearly conditions requiring therapeutic intervention. There is some amount of risk involved with the treatment or mitigation of any condition, even those as common as myopia and diabetes, but these have been minimized, and the benefits of treatment far outweigh the risks. They affect so many people in the general population that treatments have been thoroughly studied and deemed safe. But there is the recognition that even in the treatment of common conditions, there may be an individual response that should be considered when designing a treatment regimen, which falls within the scope of personalized medicine.

Personalized medicine is based on the idea that the genes you carry may increase your chances of developing a certain disease or condition, or the likelihood of a favorable response to a particular treatment. One way to accomplish this is to study a patient’s biomarkers, which can provide guidance for both diagnosing and customizing therapeutic regimens. But personalized medicine is also branching out into the study of a patient’s DNA, to attempt to predict what ailments may befall a patient before the first symptom manifests itself.

And genetic studies have potential beyond treating disease, diagnosing conditions, or even predicting who may fall ill. Personalized genomic study has the potential to identify those traits which may contribute to exceptional athletic performance and prowess. It’s not just the response to particular medications, but the response to particular workouts and diets. What if, instead of looking at where our genes may fail us, we begin to investigate where our genes may indicate a propensity for athletic ability?

And with the advent of poorly regulated direct-to-consumer DNA testing, companies are selling a look through a crystal ball. Their reports contend that you can look at someone’s genetic profile to determine an appropriate training regimen, or an ideal diet. It leads one to believe that you can detect what genetic profile makes someone more inclined to be an athlete. Genome wide association studies (GWAS) purport to provide a picture of how our personal genetics influence various physical characteristics, by first evaluating the genetic data of many people and arriving at an association between genes and traits. Companies allege that they can identify genetic markers that may explain a variety of phenotypes—that is, the external manifestation of your genetic signature. Not only do they claim to predict health risks or beneficial diets, but they claim to predict how successful you might be.

Identifying genetic markers that may be indicative of a person’s athletic ability is the goal of numerous direct-to-consumer DNA tests. Imagine if you were able to identify a particular genetic pattern that  might be an indicator of a pitcher’s durability—perhaps endurance or resilience to injury. There may be genetic markers that indicate who has increased vasculature, a higher red blood cell count, and the ability to carry more oxygen in one’s blood or to clear lactic acid more readily.

We might look for genes related to one’s metabolism, and how efficiently one can expend energy; this may come in the form of mitochondrial efficiency, and the amount of brown fat versus white fat a player has. We might look at pain perception—perhaps someone who has a higher tolerance for pain will be able to enjoy a longer career, or simply be able to pitch an additional inning per start. Maybe it’s a genetic association with fast twitch muscle fibers, which might indicate a player who’s a better base runner. Or perhaps it’s eyesight, be it depth perception, peripheral vision, or simple acuity, all of which may be helpful in identifying a pitch and making the decision of whether or not to swing. Couple that with musculature, and you could have a player who can not only see a pitch and respond accordingly, but exert the force behind the swing to drive a ball out of the park.

The problem is, a discussion of identifying and optimizing an ideal baseball player’s genome is better left to the fiction pages of The Hardball Times annual. None of this is backed by evidence yet. There’s immense potential but we have yet to see it manifested in real world data. However, the attraction of the idea that our genes are our destiny has contributed to a booming DNA testing business. Getting one’s DNA tested is low risk on the surface of it but everyone, whether a professional athlete or not, needs to be concerned with the use of that data going forward, not to mention the myriad ethical and policy questions and failings that have accompanied research like this in the past. The studies of human genes, as well as genetic testing and prediction, have a dark history, and have been and continue to be used to further a number of nefarious and prejudiced ends.

That said, someone might be willing to forgo privacy or ethical concerns if it could potentially result in a modality for performance enhancement. It’s one thing to use genetic information to attempt to predict someone’s propensity for sport, or how to enhance diet or training to thereby enhance performance. But what if, instead of just predicting your inherent capabilities or how to maximize what you already have, these genetic tests could tell you where there is room for improvement, using gene therapy?

There is very little guidance from MLB regarding the use of gene doping as a performance enhancement mechanism. Although erythropoietin (EPO) and other erythropoiesis-stimulating agents are on the prohibited substances list, there isn’t an explicit proviso against the use of gene therapy to increase red blood cell count. Jon Entine’s story of Olympic cross-country skier Eero Mdentyranta may be instructive; for years, Mdentyranta was accused of cheating. After years of allegations of blood doping, testing revealed that Mdentyranta had 15 percent more blood cells than the average man.

Entine notes, “Although Mdentyranta never failed a drug test, the rumors that he had an advantage turned out to be true. Whether the advantage was unfair depends on what you think of the gifts of fate. By 1993, Finnish researchers were able to conclude that Mdentyranta and his family carry a rare genetic mutation that produced the EPO hormone and loaded his blood cells with 50 percent more red cells than the average man’s.”

In another example of a genetic mutation that could potentially provide a performance enhancement for an athlete, the protein myostatin has been recognized as having an effect on muscle growth and development. A mutation in the gene that encodes myostatin may bypass the signal that tells muscles to stop growing, this mutation could be used to enhance athletic qualities, as Sara Chodosh observes.

“It may be that being heterozygous for a myostatin mutation just helps you become an exceptional athlete. The best racing whippets tend to have one mutated gene, and another study in Thoroughbred horses also found that the fastest sprinters often had myostatin mutations. That exceptionally strong baby’s mother turned out to be heterozygous for a mutation in the myostatin gene. She was a professional athlete, noticeably more muscular than the average woman, and she had four other relatives who were naturally strong people. It’s likely that the potential benefits of having less myostatin than normal are balanced out by the downsides of having no myostatin at all, which keeps the mutation from disappearing while also keeping us from evolving into a species of natural-born bodybuilders.”

While these are just two examples of genetics providing a human with superhuman abilities, the search for other genes that may play a role in athletic performance continues. George Church, professor of genetics at Harvard Medical School, has published a list of genes that may provide “protective, resilient, or extreme effects,” such as increased oxygen transport, enhanced learning and memory, lowered anxiety, extra strong bones, and large, lean muscles.

And here’s where things get dicey. The great promise but scant evidence associated with genetic testing, in combination with the advent of biohackers and do-it-yourself gene doping, makes this a particularly precarious time for someone looking for a quick fix. It doesn’t take a huge leap for someone to bridge the gap from gene therapy, where we’ll use a vector loaded with a fix for a faulty gene, to gene doping, where we’ll use a vector loaded with a performance enhancing gene. While the benefits may be great, there is a tremendous amount of risk and uncertainty involved, and for a baseball player who is willing to consider anything that might help him get ahead, the lustre and promise of genetic modification may blind him to the potential downfalls.

We all want to be stronger, faster, smarter. And any player who doesn’t take advantage of what’s available—be that using analytics to evaluate and modify performance, or physical interventions such as diet or specialized training—may risk losing out. But we have to work within the bounds of what’s permissible, while also bearing in mind modifications and habits which are backed by scientific evidence. The lack of evidence both in terms of what’s actually effective, and what’s clearly not, in combination with an athlete’s desire to perform at a highly competitive level for as long as possible, makes this area ripe for the misuse of pharmaceuticals, nutraceuticals, and technology.

While I can’t answer the question of what the next performance enhancing substance will be, it is clear that the use of genetic profiling and gene doping will play a role in the next frontier in performance enhancement. Regardless of whether any of it works, we need to take a more proactive approach when evaluating the role of genomics in professional sport. With recent reports that a scientist in China has brought genetically edited babies (also known as the CRISPR babies) into the world, we need to ask ourselves when performance enhancement starts.

If we gauge performance enhancement by what is “normal,” we need to consider what “normal” means, and recognize that “normal” itself may be a moving target. We recognize that certain inherent conditions should be treated, but we also need to recognize that this correction may result in enhanced performance in one way or another. If  parents decide to have their fetus edited so that it carries genes that may make the baby a better baseball player, are we going to deny that kid the chance to play baseball? Ultimately, there is no clear definition of what enhancement entails. George Church notes, “almost anything is possible; the question is: What would be welcomed by sports rule committees?”

We’re not going to see CRISPR baseball players anytime soon, but as with the definitions of “performance” and “enhancement,” it’s something sports rule committees need to consider now, with the guidance of bioethicists.

References and Resources

• Kevin Loria, “Harvard researchers have identified gut bacteria that help athletes — and plan to make them available to everyone in supplements,” Business Insider, August 23, 2017
• Jef Akst, “Athletes’ Microbiomes Differ from Nonathletes,” The Scientist, June 2017
• Ryan Mandelbaum, “Athlete Poop Won’t Improve Your Athletic Performance,” Gizmodo, June 30, 2017
• Kevin Loria, “Companies are trying to use your DNA and bacteria to give you personalized diet advice — here’s what the science says,” Business Insider, June 11, 2017
• Jeff Zimmerman, “A Primer on Tommy John Surgery,” The Hardball Times, June 2014
• James Andrews, et al., “The Ulnar Collateral Ligament Procedure Revisited,” Sports Health, 2012, vol. 4, no. 5, pages 438-41
• Kevin Mitchell, “Is Our Future Really Written in Our Genes?” Scientific American, January 2019
• Eric Niiler, “Olympic Drug Cops Will Scan Genetically Modified Athletes,” Wired, July 28, 2016
• Sara Chodosh, “Why these animals (and one baby) are incredibly jacked,” Popular Science, January 11, 2019
• Helen Thompson, “Performance enhancement: Superhuman athletes” Nature, July 18, 2012